scholarly journals Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Polymers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1872 ◽  
Author(s):  
Rishi Thakkar ◽  
Amit Raviraj Pillai ◽  
Jiaxiang Zhang ◽  
Yu Zhang ◽  
Vineet Kulkarni ◽  
...  
Keyword(s):  
Drug Release ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous State ◽  
Dosage Forms ◽  
Water Soluble ◽  
Patient Specific ◽  
3 Dimensional ◽  
Fused Deposition ◽  
3D Printed ◽  
The Impact

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

scholarly journals O22 3D printed polyethylene oxide oral doses with innovative ‘radiator-like’ design: impact of molecular weight on mechanical and rheological properties and drug release

2019 ◽  
Vol 104 (6) ◽  
pp. e10.1-e10 ◽  
Author(s):  
M Peak ◽  
K Baj ◽  
A Isreb ◽  
M Wojsz ◽  
I Mohammad ◽  
...  
Keyword(s):  
Molecular Weight ◽  
3D Printing ◽  
Drug Release ◽  
Rheological Properties ◽  
Oral Dosage ◽  
Parallel Plates ◽  
Fused Deposition ◽  
Plate Spacing ◽  
3D Printed ◽  
The Impact

BackgroundDespite regulatory advances, lack of age-appropriate formulations (AAFs) remains a challenge in paediatric practice. 3D-printing of oral dosage forms (ODFs) offers potential for AAFs for children. Optimising drug release from 3D-printed ODFs is an important technological step. Despite the abundant use of polyethylene oxides (PEOs) and their extensive use as an excipient, there have been no previous reports of applying this thermoplastic polymer species alone to fused deposition modelling (FDM) 3D printing. We assessed the impact of polymer molecular weight (MW) on the mechanical properties of the resultant filaments and their rheological properties. In the FDM 3D printing process, we also tested the effect of an innovative radiator-like design of the ODF on the acceleration of drug release patterns.MethodsBlends of PEO (MW: 100K, 200K, 300K, 600K or 900K) with PEG 6K (plasticiser) and a model drug (theophylline) were prepared by hot-melt extrusion. The resultant filaments were used as a feed for a FDM 3D printer to fabricate innovative designs of ODFs in a radiator-like geometry with inter-connected paralleled plates and inter-plate spacing of either 0.5mm, 1mm, 1.5mm or 2mm.ResultsVarying blends of PEO and PEG allowed formation of mechanically resistant filaments (maximum load at break of 357, 608, 649, 882, 781 N for filament produced with 100K, 200K, 300K, 600K or 900K, respectively). Filaments of PEO at a MW of 200K-600K were compatible with FDM 3D printing. Further increase in PEO MW resulted in elevated shear viscosity (>104 Pa.S) at the printing temperature and hindered material flow during FDM 3D printing. A minimum spacing (1 mm) between parallel plates of the radiator-like design was essential to boost drug release from the structure.ConclusionThese findings are essential in the development of next-generation personalised drug delivery doses using specialised polymer/polymer blends purposely optimised for FDM 3D printing.Disclosure(s)Nothing to disclose

scholarly journals Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1453
Author(s):  
Hellen Windolf ◽  
Rebecca Chamberlain ◽  
Julian Quodbach
Keyword(s):  
Drug Release ◽  
Surface Area ◽  
Volume Ratio ◽  
Dosage Forms ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Alcohol Water ◽  
Wide Range ◽  
3D Printed ◽  
Release Profiles

3D printing offers the advantage of being able to modify dosage form geometry, which can be exploited to modify release characteristics. In this study, we investigated the influence of the surface area to volume ratio (SA/V) to change and predict release profiles of 3D printed dosage forms. Geometries with varying SA/V and dosages were designed and printed, and drug dissolution was investigated. Three drug substances were used: pramipexole, levodopa (both BCS I) and praziquantel (BCS II). Two polymers were chosen as matrix formers: polyvinyl alcohol (water-soluble) and ethylene vinyl acetate (inert). Drug release was characterized using the mean dissolution time (MDT) and established equations that describe complete dissolution curves were applied. Predictions were validated with previously un-printed dosage forms. Based on an identified MDT-SA/V correlation, the MDT can be predicted with a deviation of ≤5 min for a given SA/V. Using correlations of fit parameters and SA/V, RMSEP values of 0.6–2.8% and 1.6–3.4% were obtained for the BCS I formulations and RMSEP values of 1.0–3.8% were obtained for the BCS II formulation, indicating accurate prediction over a wide range of dissolution profiles. With this approach, MDT and release profiles of dosage forms with a given SA/V can be precisely predicted without performing dissolution tests and vice versa, the required SA/V can be predicted for a desired release profile.

scholarly journals Patient-Specific 3-Dimensional Printed Models for Planning Nasal Osteotomy to Correct Nasal Deformities Due to Trauma

OTO Open ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. 2473974X2092434
Author(s):  
Yong Gi Jung ◽  
Hanaro Park ◽  
Jiwon Seo
Keyword(s):  
Fused Deposition Modeling ◽  
Nasal Bone ◽  
Patient Specific ◽  
3 Dimensional ◽  
Fused Deposition ◽  
Computed Tomography Images ◽  
Real Size ◽  
Deposition Modeling ◽  
3D Printed ◽  
3D Printing Technique

Nasal deformities due to trauma are more challenging to correct with rhinoplasty than nasal deformities of nontraumatic causes. Nasal osteotomy is an essential procedure for bone deviations. Preoperative planning is vital in these cases, but it is challenging to comprehend 3-dimensional (3D) structures of the nasal bone on 2-dimensional facial photographs and computed tomography images. We used a 3D-printing technique to fabricate real-size facial bone models with similar physical properties and texture as the actual bone. Furthermore, we established a precise surgical plan using simulated osteotomy on the 3D-printed model. Fused deposition modeling–type desktop 3D printer with polylactic acid filaments was used. A surgical plan was established using simulated osteotomy in 11 cases, and the actual surgery was performed as planned in 10 cases (90.9%). The 3D-printed model and stimulated osteotomy were useful for precise planning of osteotomy to correct nasal deformities due to trauma.

scholarly journals Polyvinyl Alcohol-Based 3D Printed Tablets: Novel Insight into the Influence of Polymer Particle Size on Filament Preparation and Drug Release Performance

2021 ◽  
Vol 14 (5) ◽  
pp. 418
Author(s):  
Andrea Gabriela Crișan ◽  
Alina Porfire ◽  
Rita Ambrus ◽  
Gábor Katona ◽  
Lucia Maria Rus ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Polyvinyl Alcohol ◽  
Fused Deposition Modeling ◽  
Dosage Forms ◽  
Solid Dosage Forms ◽  
Manufacturing Method ◽  
Solid Dosage ◽  
Fused Deposition ◽  
3D Printed

Three-dimensional printing (3DP) by fused deposition modeling (FDM) has gained momentum as a promising pharmaceutical manufacturing method due to encouraging forward-looking perspectives in personalized medicine preparation. The current challenges the technology has for applicability in the fabrication of solid dosage forms include the limited range of suitable pharmaceutical grade thermoplastic materials. Hence, it is important to investigate the implications of variable properties of the polymeric carrier on the preparation steps and the final output, as versatile products could be obtained by using the same material. In this study, we highlighted the influence of polyvinyl alcohol (PVA) particle size on the residence time of the mixtures in the extruder during the drug-loaded filament preparation step and the consequent impact on drug release from the 3D printed dosage form. We enhanced filament printability by exploiting the plasticizing potential of the active pharmaceutical ingredient (API) and we explored a channeled tablet model as a design strategy for dissolution facilitating purposes. Our findings disclosed a new perspective regarding material considerations for the preparation of PVA-based solid dosage forms by coupling hot melt extrusion (HME) and FDM-3DP.

scholarly journals 3D-Printed Isoniazid Tablets for the Treatment and Prevention of Tuberculosis—Personalized Dosing and Drug Release

2019 ◽  
Vol 20 (2) ◽  
Author(s):  
Heidi Öblom ◽  
Jiaxiang Zhang ◽  
Manjeet Pimparade ◽  
Isabell Speer ◽  
Maren Preis ◽  
...  
Keyword(s):  
3D Printing ◽  
Drug Release ◽  
Oral Drug Delivery ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Oral Drug ◽  
Fused Deposition ◽  
3D Printed ◽  
Hot Melt ◽  
Release Profiles

Abstract The aim of the present work was to produce 3D-printed oral dosage forms with a sufficient drug dose displaying various release profiles. Hot-melt extrusion was utilized to produce drug-loaded feedstock material that was subsequently 3D-printed into 6, 8, and 10 × 2.5 mm tablets with 15% and 90% infill levels. The prepared formulations contained 30% (w/w) isoniazid in combination with one or multiple pharmaceutical polymers possessing suitable properties for oral drug delivery. Thirteen formulations were successfully hot-melt extruded of which eight had properties suitable for fused deposition modeling 3D printing. Formulations containing HPC were found to be superior regarding printability in this study. Filaments with a breaking distance below 1.5 mm were observed to be too brittle to be fed into the printer. In addition, filaments with high moisture uptake at high relative humidity generally failed to be printable. Different release profiles for the 3D-printed tablets were obtained as a result of using different polymers in the printed formulations. For 8 mm tablets printed with 90% infill, 80% isoniazid release was observed between 40 and 852 min. Drug release characteristics could further be altered by changing the infill or the size of the printed tablets allowing personalization of the tablets. This study presents novel formulations containing isoniazid for prevention of latent tuberculosis and investigates 3D printing technology for personalized production of oral solid dosage forms enabling adjustable dose and drug release properties.

scholarly journals Oral drug delivery systems using core–shell structure additive manufacturing technologies: a proof-of-concept study

2021 ◽  
Author(s):  
Jiaxiang Zhang ◽  
Pengchong Xu ◽  
Anh Q Vo ◽  
Michael A Repka
Keyword(s):  
Drug Delivery ◽  
3D Printing ◽  
Drug Release ◽  
Water Soluble ◽  
Oral Drug ◽  
Core Shell ◽  
Fluid Medium ◽  
Fused Deposition ◽  
Enhanced Solubility ◽  
3D Printed

Abstract Objectives The aim of this study was to couple fused deposition modelling 3D printing with melt extrusion technology to produce core–shell-structured controlled-release tablets with dual-mechanism drug-release performance in a simulated intestinal fluid medium. Coupling abovementioned technologies for personalized drug delivery can improve access to complex dosage formulations at a reasonable cost. Compared with traditional pharmaceutical manufacturing, this should facilitate the following: (1) the ability to manipulate drug release by adjusting structures, (2) enhanced solubility and bioavailability of poorly water-soluble drugs and (3) on-demand production of more complex structured dosages for personalized treatment. Methods Acetaminophen was the model drug and the extrusion process was evaluated by a series of physicochemical characterizations. The geometries, morphologies, and in vitro drug-release performances were compared between directly compressed and 3D-printed tablets. Key findings Initially, 3D-printed tablets released acetaminophen more rapidly than directly compressed tablets. Drug release became constant and steady after a pre-determined time. Thus, rapid effectiveness was ensured by an initially fast acetaminophen release and an extended therapeutic effect was achieved by stabilizing drug release. Conclusions The favourable drug-release profiles of 3D-printed tablets demonstrated the advantage of coupling HME with 3D printing technology to produce personalized dosage formulations.

scholarly journals Quality Control in 3D Printing: Accuracy Analysis of 3D-Printed Models of Patient-Specific Anatomy

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 1021
Author(s):  
Bernhard Dorweiler ◽  
Pia Elisabeth Baqué ◽  
Rayan Chaban ◽  
Ahmed Ghazy ◽  
Oroa Salem
Keyword(s):  
Wall Thickness ◽  
Large Scale ◽  
Fused Deposition Modeling ◽  
Vascular Anatomy ◽  
3D Models ◽  
Patient Specific ◽  
Stl File ◽  
Fused Deposition ◽  
3D Printed ◽  
The Mean

As comparative data on the precision of 3D-printed anatomical models are sparse, the aim of this study was to evaluate the accuracy of 3D-printed models of vascular anatomy generated by two commonly used printing technologies. Thirty-five 3D models of large (aortic, wall thickness of 2 mm, n = 30) and small (coronary, wall thickness of 1.25 mm, n = 5) vessels printed with fused deposition modeling (FDM) (rigid, n = 20) and PolyJet (flexible, n = 15) technology were subjected to high-resolution CT scans. From the resulting DICOM (Digital Imaging and Communications in Medicine) dataset, an STL file was generated and wall thickness as well as surface congruency were compared with the original STL file using dedicated 3D engineering software. The mean wall thickness for the large-scale aortic models was 2.11 µm (+5%), and 1.26 µm (+0.8%) for the coronary models, resulting in an overall mean wall thickness of +5% for all 35 3D models when compared to the original STL file. The mean surface deviation was found to be +120 µm for all models, with +100 µm for the aortic and +180 µm for the coronary 3D models, respectively. Both printing technologies were found to conform with the currently set standards of accuracy (<1 mm), demonstrating that accurate 3D models of large and small vessel anatomy can be generated by both FDM and PolyJet printing technology using rigid and flexible polymers.

scholarly journals The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 455
Author(s):  
Emilia Szymańska ◽  
Katarzyna Woś-Latosi ◽  
Julia Jacyna ◽  
Magdalena Dąbrowska ◽  
Joanna Potaś ◽  
...  
Keyword(s):  
Drug Release ◽  
Polymer Matrix ◽  
Drug Loading ◽  
Water Soluble ◽  
Dissolution Behavior ◽  
Complex Nature ◽  
Prolonged Release ◽  
Scanning Calorimetry ◽  
Burst Effect ◽  
The Impact

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

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